We have investigated the interaction of carcinogens with DNA of human fibroblasts and the effect of DNA repair on this interaction. Diploid human cells offer a unique advantage because of their high rates of excision repair and the availability of repair deficient XP strains. We have demonstrated that if repair proficient cells are prevented from replicating, but allowed to excise, they can eliminate potentially lethal and mutagenic effects of carcinogens. We have developed quantitative methods to measure the rate of repair replication and the removal of specific carcinogen residues covalently bound to DNA. The rate of excision determines the ultimate cytotoxic effect of carcinogens and the number of unexcised lesions remaining at the time semi-conservative DNA replication takes place ultimately determines the mutagenic effect of the damage. Because genetically altered cell characteristics may be responsible for the initiation of malignant transformation, we propose to investigate: 1) The kinetics of excision repair induced by different carcinogens, the number and kind of adducts removed, the nature of the excised region, and whether these adducts cause significant distortion of the DNA in order to correlate these with the biological consequences of carcinogen treatment; 2) The critical relationship between the rate of excision repair, the length of cell cycle, and the biological effects of carcinogens; 3) The postreplication repair mechanisms used by human cells to cope with unexcised damage; 4) Whether the carcinogenic potency of a series of structurally-related polycyclic hydrocarbons is correlated with differences in rates of metabolism, rates of binding to DNA, rates of excision repair, or intrinsic mutagenic potency of particular DNA adducts.